The project concerns how humans perceive irritation, a chemesthetic sensation, in the upper airways and eyes. As a sense modality, chemesthesis registers inter alia the presence of nonreactive volatile organic compounds (VOCs), i.e., those not immediately corrosive to tissue. Such materials, many of them solvents, occur in indoor environments and the work place, where irritation often justifies exposure limits. The overarching goal of the research is to predict irritation from knowledge of the physicochemical properties of a VOC, the site and duration of exposure to it, and the condition of the mucosa. The research in this program will seek: 1) To elucidate the role of duration of stimulation on responses to VOCs, with particular focus upon how duration of exposure amplifies sensitivity. 2) To test objective correlates of chemesthetic sensations: a) motor reactions, viz., strain from contractions of the orbicularis oculi, and b) neurophysiological potentials, viz., the negative mucosal potential (NMP). 3) To predict and test linear free-energy relationships (LFERs) that account for potency in terms of solute-solvent interactions. Insofar as the role of duration on potency (Aim 1) becomes known, the parameter of time can be added to the LFER. 4) To establish how much leverage mucosal inflammation has to amplify sensitivity to VOCs. Psychophysical and neurophysiological experiments with normal subjects and persons with allergic rhinitis will test six hypotheses. Upon completion of the experiments, the following should be known: A) How long it takes to evoke chemesthesis from VOCs and the degree to which this differs among them. B) Whether mass or some other combination of concentration x time is the effective stimulus for chemesthesis to VOCs. C) Through use of a functional measure, how well chemesthesis can be read non-invasively and even without a subject's need to attend to stimulation. E) An LFER that incorporates time and thereby accounts for additional effects by non-neural, physicochemical parameters. F) The effect of inflammation upon chemesthetic sensitivity. G) Through measurement of the NMP, confirmation of the peripheral basis for a) temporal phenomena, b) differences in potency, and c) effects of inflammation.